S-Nitrosation of monocarboxylate transporter 1: inhibition of pyruvate-fueled respiration and proliferation of breast cancer cells. Free Radic Biol Med 2014 Apr;69:229-38
Date
02/04/2014Pubmed ID
24486553Pubmed Central ID
PMC3982622DOI
10.1016/j.freeradbiomed.2014.01.031Scopus ID
2-s2.0-84894240371 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Energy substrates metabolized through mitochondria (e.g., pyruvate, glutamine) are required for biosynthesis of macromolecules in proliferating cells. Because several mitochondrial proteins are known to be targets of S-nitrosation, we determined whether bioenergetics are modulated by S-nitrosation and defined the subsequent effects on proliferation. The nitrosating agent S-nitroso-L-cysteine (L-CysNO) was used to initiate intracellular S-nitrosation, and treatment decreased mitochondrial function and inhibited proliferation of MCF7 mammary adenocarcinoma cells. Surprisingly, the d-isomer of CysNO (D-CysNO), which is not transported into cells, also caused mitochondrial dysfunction and limited proliferation. Both L- and D-CysNO also inhibited cellular pyruvate uptake and caused S-nitrosation of thiol groups on monocarboxylate transporter 1, a proton-linked pyruvate transporter. These data demonstrate the importance of mitochondrial metabolism in proliferative responses in breast cancer and highlight a novel role for inhibition of metabolic substrate uptake through S-nitrosation of exofacial protein thiols in cellular responses to nitrosative stress.
Author List
Diers AR, Broniowska KA, Chang CF, Hill RB, Hogg NAuthor
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell ProliferationCell Respiration
Cysteine
Humans
MCF-7 Cells
Mitochondria
Monocarboxylic Acid Transporters
Nitric Oxide
Nitrosation
Pyruvic Acid
S-Nitrosothiols
Sulfhydryl Compounds
Symporters
